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REVIEW PAPER

Integrative review: postcraniotomy pain in the brain tumour patient

Rebecca Elizabeth Guilkey, Diane Von Ah, Janet S. Carpenter, Cynthia Stone & Claire B. Draucker

Accepted for publication 17 November 2015

Correspondence to R.E. Guilkey:

e-mail: [email protected]

Rebecca Elizabeth Guilkey PhD(c) RN

CCRN

PhD Candidate

Indiana University School of Nursing,

Indianapolis, Indiana, USA

Diane Von Ah PhD FAAN RN

Assistant Professor

Indiana University School of Nursing,

Indianapolis, Indiana, USA

Janet S. Carpenter PhD FAAN RN

Distinguished Professor and Associate Dean

for Research and Scholarship

Indiana University School of Nursing,

Indianapolis, Indiana, USA

Cynthia Stone DrPH RN

Associate Professor and Director of Health

Policy Management Doctoral Program

Indiana University Fairbanks School of

Public Health, Indianapolis, Indiana, USA

Claire B. Draucker PhD FAAN RN

Angela Barron McBride Endowed Professor

in Mental Health Nursing

Indiana University School of Nursing,

Indianapolis, Indiana, USA

GUILKEY R . E . , VON AH D . , CARPENTER J . S . , STONE C . & DRAUCKER C .B .

( 2 0 1 6 ) Integrative review: postcraniotomy pain in the brain tumour patient. Jour-

nal of Advanced Nursing 72(6), 1221–1235. doi: 10.1111/jan.12890

Abstract Aim. To conduct an integrative review to examine evidence of pain and

associated symptoms in adult (≥21 years of age), postcraniotomy, brain tumour

patients hospitalized on intensive care units.

Background. Healthcare providers believe craniotomies are less painful than

other surgical procedures. Understanding how postcraniotomy pain unfolds over

time will help inform patient care and aid in future research and policy

development.

Design. Systematic literature search to identify relevant literature. Information

abstracted using the Theory of Unpleasant Symptoms’ concepts of influencing

factors, symptom clusters and patient performance. Inclusion criteria were

indexed, peer-reviewed, full-length, English-language articles. Keywords were

‘traumatic brain injury’, ‘pain, post-operative’, ‘brain injuries’, ‘postoperative

pain’, ‘craniotomy’, ‘decompressive craniectomy’ and ‘trephining’.

Data sources. Medline, OVID, PubMed and CINAHL databases from

2000–2014.

Review method. Cooper’s five-stage integrative review method was used to assess

and synthesize literature.

Results. The search yielded 115 manuscripts, with 26 meeting inclusion criteria.

Most studies were randomized, controlled trials conducted outside of the United

States. All tested pharmacological pain interventions. Postcraniotomy brain

tumour pain was well-documented and associated with nausea, vomiting and

changes in blood pressure, and it impacted the patient’s length of hospital stay,

but there was no consensus for how best to treat such pain.

Conclusion. The Theory of Unpleasant Symptoms provided structure to the

search. Postcraniotomy pain is experienced by patients, but associated symptoms

and impact on patient performance remain poorly understood. Further research is

needed to improve understanding and management of postcraniotomy pain in this

population.

Keywords: brain tumour, craniotomy, integrative review, literature review,

nurses, nursing, pain, theory of unpleasant symptoms

info:doi/10.1111/jan.12890

Introduction

Background

Brain tumour is the seventeenth-most diagnosed cancer

worldwide, with 256,000 new cases of brain tumour diag-

nosed in 2012. Men suffer from brain cancer slightly more

frequently than women (Bondy et al. 2008, World Cancer

Research Fund International 2013, Central Brain Tumor

Registry of the United States 2014, Ferlay et al. 2015) and

incidence rates are higher in developed countries than in

lesser developed countries (Bondy et al. 2008, World Can-

cer Research Fund International 2013, Central Brain Tumor

Registry of the United States 2014). Scientific advances have

resulted in improvements in the diagnosis and treatment of

brain tumours (Bondy et al. 2008). In fact, 1- and 5-year

survival rates have increased from 7�3% in 1970 to over 18% in 2011 (Informational Services Division of the

National Health Services 2010, Cancer Research UK 2014,

Ferlay et al. 2015, Queen’s University Belfast 2015).

Approximately 90% of patients with brain tumours

undergo craniotomies for excision and removal of the

tumour to increase survival (National Cancer Institute

2014). Surgical procedures are generally understood to be

painful (McCaffery & Pasero 1999) but less is understood

about postcraniotomy pain. Healthcare providers commonly

believe that craniotomies are less painful than other types of

surgery due to lack of innervation in the brain (Hassouneh

et al. 2010, American Brain Tumor Association 2012) and

are thus less apt to treat pain. In addition, postcraniotomy

pain is often untreated or undertreated due to concerns that

it may mask neurological changes in these patients (Talke &

Gelb 2005, Durieux & Himmelseher 2007, Lai et al. 2012).

Pain is often associated with other symptoms including anxi-

ety and depression (McCaffery & Pasero 1999, Rocha-Filho

2015) and nausea and/or vomiting (Dolin & Cashman

2005). Understanding postcraniotomy pain in brain tumour

patients is important because postoperative pain is a com-

mon cause of delayed mobilization (Saha et al. 2013),

lengthened hospital stay (Chung et al. 1997, Casler et al.

2005, Saha et al. 2013), disability and decreased quality of

life (Andrasik et al. 2011, O’Connor & Dworkin 2011). In

addition, research has shown that under-treated, generalized

postoperative pain is a predictor of the development of per-

sistent pain (Macrae 2001, Dobrogowski et al. 2008, Watt-

Watson & McGillion 2011, Wu & Raja 2011, Lamacraft

2012). To date, postcraniotomy pain and the symptoms

associated with it is poorly understood. Researchers have

called for additional studies to understand influencing fac-

tors and associated symptoms of postcraniotomy pain and to

determine how to best treat it to prevent negative health out-

comes (Talke & Gelb 2005, Roberts 2005, Watson 2011,

De Oliveira Ribeiro et al. 2013, Rocha-Filho 2015).

Definitions and theory

The International Society for the Study of Pain describes

pain as a subjective sensory and emotional experience

(McCaffery & Pasero 1999, Watt-Watson & McGillion

2011, Gelinas et al. 2013). Pain is a complex symptom com-

prised of at least four dimensions (intensity, affect, quality

and location) (Puntillo et al. 2002, Jensen & Karoly 2011).

Physical, psychological, social and cultural factors influence

the experience of pain (Melzack 1999, Saha et al. 2013).

The Theory of Unpleasant Symptoms (TOUS), which

suggests that symptoms such as pain are multidimensional

and interactive, is commonly used to support pain research,

because it is relevant to practice and can be used as a

Why is this research or review needed?

� Brain tumour patients have long been believed to experi- ence little pain postcraniotomy due to lack of innervation

in the brain.

� Understanding symptoms correlated with postcraniotomy pain in brain tumour patients will help healthcare provi-

ders provide better treatment.

� Addressing untreated and undertreated postcraniotomy pain will improve patient-centred outcomes and quality of

life.

What are the key findings?

� Postcraniotomy patients experience significant levels of pain, but current treatment of postcraniotomy pain lacks

evidence-based guidelines.

� Postcraniotomy pain in brain tumour patients may be asso- ciated with nausea, vomiting and changes in blood pres-

sure and may play a role in health care use such as longer

hospital stays.

How should the findings be used to influence policy/ practice/research/education?

� Understanding the manner in which postcraniotomy pain unfolds should inform healthcare providers’ recognition of

the symptom.

� Recognition of the intensity of postcraniotomy pain and its impact should lead to timely treatment of the symptom

and improve patient outcomes.

R.E. Guilkey et al.

framework for making decisions related to patient care

(Myers 2009, Lenz et al. 2013). The TOUS includes three

main concepts: (1) physiological, measureable symptoms

experienced by the patient; (2) influencing factors which

alter the patient’s experience of the symptom and (3)

patient performance (Lenz et al. 1997, 2013). Influencing

factors are physiological, psychological and situational in

nature and can catalyse each other affecting patient perfor-

mance (Lenz et al. 1997, 2013). Performance is the impact

of the symptom on patient outcomes including functional

performance (the ability to physically function) and cogni-

tive performance (the ability to think) (Lenz et al. 1997,

2013). Researchers using the TOUS have termed groups of

associated symptoms as ‘clusters’ (Lenz et al. 1997). This

review will also use the term cluster to identify these groups

of co-related symptoms.

The review

Aim

The aim of this study was to conduct an integrative review

using the TOUS as a guiding framework to synthesize and

examine what is known about the phenomenon of pain in

adult (≥21 years of age), postcraniotomy, brain tumour

patients. Specifically, this review sought to answer the

following research questions: (1) What is the evidence for

postcraniotomy, postbrain tumour pain in adult (≥21 years

of age) patients hospitalized on intensive care units?; and

(2) What is the evidence for a postcraniotomy symptom

cluster associated with pain in adult (≥21 years of age)

patients hospitalized on intensive care units?

Design

Cooper’s (2010) integrative review method guided the

review. This method of integrative review was chosen

because it provides a systematic framework to synthesize the

current literature about postcraniotomy pain in the brain

tumour patient (Whittemore & Knafl 2005, Cooper 2010).

Cooper’s method includes five stages: advance formulation of

the problem, data collection, data extraction, evaluation,

analysis and interpretation (Cooper 2010). The formulation

of the problem, the first stage of the method, was informed

by a preliminary literature search and the researchers’ clinical

experience that suggested a greater understanding of acute

postcraniotomy pain was warranted. The authors felt an inte-

grative review was necessary to synthesize the current litera-

ture and further the state of the science (Whittemore & Knafl

2005, Cooper 2010).

Search methods

Data collection, the second stage, consisted of a literature

search. Studies were identified for inclusion by purposive

searching of electronic databases including Medline, OVID,

PubMed and CINAHL. In addition, hand-searching of ref-

erences and an examination of citations from identified

published reviews were conducted. Two experienced

reference librarians provided consultation on the search

process. Search terms for all databases and searches

included traumatic brain injury; pain, postoperative; brain

injuries; postoperative pain; craniotomy; decompressive

craniectomy; and trephining. Inclusion criteria were as fol-

lows: (1) data-based quantitative and qualitative articles

focused on postcraniotomy pain in adult brain tumour

patients aged 21 or older; (2) published between 1 January

2000–12 December 2014; (3) English-language; (4) neuro-

surgical inpatients and (5) intensive care unit settings.

Abstracts, editorials, dissertations, theses, reviews and

articles concerning intraoperative pain control, end-of-life

care, or institutional practices were excluded.

Search outcome

The search strategy generated 115 studies. The studies

which were recorded in a Preferred Reporting Items for Sys-

tematic Review and Meta-Analyses (PRISMA) diagram

(Figure 1). A total of 109 potentially relevant studies

remained after the initial screening of titles for duplicates,

publication in English and publication dates. The remaining

abstracts were reviewed for type of study, population, study

setting and discussion of pain. After application of the

inclusion and exclusion criteria, we eliminated 83 addi-

tional articles from review, including five qualitative studies

that either did not meet inclusion criteria because they did

not focus on pain or the participants were not inpatients.

This resulted in a sample of 26 quantitative articles to be

reviewed in full-text format (Table 1). Data from eligible

studies were abstracted into tables listing general informa-

tion, level of evidence and concepts defined in the TOUS.

Quality appraisal

In the third stage, two authors completed a quality apprai-

sal on the 26 articles. Using a 3-point scale (yes, no,

unclear) described by Gazarian, they rated the studies on

nine criteria including aims, design, methods, sample,

ethical considerations, results, limitations, implications and

sponsorship (2013). The studies were also appraised for

bias using the Cochrane Risk of Bias tool. Twenty-one of

JAN: REVIEW PAPER Integrative review – postcraniotomy pain

the studies used a randomized design. Of the five studies

that did not use randomization, two were retrospective

(Thibault et al. 2007, Ducic et al. 2012) and three were

prospective trials (Irefin et al. 2003, Grossman et al. 2007,

Nair & Rajshekhar 2011). The team determined that these

five studies nonetheless met inclusion criteria and thus all

26 studies are included in the review.

Data abstraction

The fourth stage includes data analysis and interpretation

(Cooper 2010). In this stage, all of the included studies

were read in full and relevant data were extracted and tab-

ulated. Table 1 displays the authors’ names; dates and

countries of publication; purpose and design; sample, set-

ting and intervention; medication tested; and pain preva-

lence, incidence and intensity. (Table 1).

Data synthesis

In the fifth and final stage, the tabulated data were synthe-

sized to address the research questions (Cooper 2010). The

authors grouped the data into categories suggested by the

TOUS including incidence of pain, influencing factors, cluster

and patient performance (Table 2). Two of the authors (RG

&DVA) reviewed each study and verified the accuracy of data

as presented and over several meetings compiled the results.

Results

Description of the studies

Of the 26 studies included, all were pharmacological pain

management trials (pain medications) and most were ran-

domized, controlled trials (RCTs) (n = 21). The studies

included 1892 total patients and were originally designed to

test local wound infiltration or medications to control pain

(intravenous, intramuscular, oral medications, nerve blocks,

general anaesthesia) (Table 1). The medications that were

tested varied but mostly included bupivacaine, ropivacaine,

tramadol, parecoxib, paracetamol and morphine.

The mean ages of the participants in the studies ranged

from 45-55 and approximately equal numbers of men and

women were represented. The comprehensive search identi-

fied five qualitative studies; however, these did not meet

inclusion criteria (focus not on pain or participants not

inpatients) and were excluded from final analysis. The

majority of trials took place outside of the United States at

non-profit, urban, academic medical institutions. Only one

study reported racial characteristics of the sample that con-

sisted mostly of Caucasians (52 vs. 12 non-Caucasian)

(Morad et al. 2009). Reports included both supratentorial

surgeries and infratentorial surgeries with mean lengths of

surgery ranging between 200 and 300 minutes.

115 total papers screened from

electronic search of 4 databases (OVID

Medline, Nursing @ OVID, PubMed, and

CINAHL) 6 articles excluded for not meeting inclusion criteria (duplicates, not published

in English, published prior to 2000)

83 articles excluded for not meeting inclusion

criteria: 27 not solely brain tumor population

16 not pain focused 11 traumatic brain injury 8 pediatric/adolescent 6 technique/procedure

focused 5 not postoperative

5 review 4 healthcare staff focus

1 letter to editor

109 potentially relevant citations

identified

26 articles to be reviewed in full-text

format

Figure 1 PRISMA diagram of systematic search.

R.E. Guilkey et al.

Table 1 Summarization of studies.

Author, year, Country Design, sample size, medication Existence of pain and pain intensity, rating scale used

Bala et al. (2006)

India

Prospective, double-blind RCT; N = 40

Medication: Scalp nerve block (bupivacaine)

60% experienced moderate-severe pain in first

12 hours post-op (control)

25% experienced moderate-severe pain in first

12 hours post-op (intervention)

Rating Scale: NRS; scores 0-22�5 out of 100 Batoz et al. (2009)

France

Prospective, single-blinded study; N = 52

Medication: Incisional infiltration (ropivacaine);

nalbuphine postsurgery

VAS scores higher in control group

Persistent pain significantly lower in intervention

group at 2 months (56% in control group vs. 8%

in intervention group)

Rating Scale: VAS; scores 0-35 out of 50

Biswas and

Bithal (2003)

India

Prospective, double-blind RCT; N = 50

Medication: Incisional infiltration (bupivacaine)

vs. fentanyl

Additional medication needed in 60% of

bupivacaine group and 57% of fentanyl group

Rating Scale: VAS; scores 0-4 out of 10

Ducic et al. (2012)

United States

Retrospective interview of patients; N = 7

Medication: None tested

86% experienced pain greater than 80% on

migraine index

Rating Scale: VAS; scores 2-10 out of 10

Ferber et al. (2000)

Poland

Multi-stage prospective study; N = 35

Medication: Intravenous tramadol

Pain relief in 50% of patients receiving one dose;

in 88% of patients receiving 2 or 3 doses

Rating Scale: VRS; scores 0-4 out of 5

Girard et al. (2010)

Canada

Prospective, double-blind RCT; N = 30

Medication: Cervical plexus nerve block

(lidocaine and bupivacaine) vs. intravenous

morphine bolus

Similar pain scores between nerve block and

morphine groups

Rating Scale: NRS; scores 2-7 out of 10

Grossman et al. (2007)

Israel

Open, prospective, double-blind non-randomized,

placebo- controlled study; N = 40

Medication: Incisional infiltration (lidocaine and

bupivacaine); metamizol intra-operatively

13 patients needed additional pain medication

Rating Scale: NRS; scores 0-4 out of 10

Irefin et al. (2003)

United States

Prospective study; N = 128

Medication: None tested

No significant difference in pain scores between

groups

Rating Scale: VAS; scores 0-5 out of 10

Jellish et al. (2006)

United States

Prospective, double-blind RCT; N = 120

Medication: PCA (morphine or morphine plus

ondansetron)

Up to 76% experienced post-op pain

Administered analgesia was inadequate

Rating Scale: VAS; scores 4�5-6�1 out of 10 Jones et al. (2009)

Australia

Prospective, double-blind RCT; N = 50

Medication: Intravenous parecoxib; morphine

postoperatively

89% of patients required additional pain

medication (morphine)

Pain scores significantly lower in parecoxib group

only at 6 hours

Rating Scale: VAS; scores 0-35 out of 100

Law-Koune et al. (2005)

France

Prospective, double-blind RCT; N = 80

Medication: Incisional infiltration (bupivacaine

plus epinephrine) vs. ropivacaine

Placebo group received more morphine than

bupivacaine or ropivacaine groups (22�2 mg; 12�7 mg; 10�5 mg respectively) Rating Scale: VAS; scores 0-7 out of 10

Magni et al. (2005)

Italy

Prospective, randomized, open-label clinical trial;

N = 120

Medication: General anaesthesia

(sevoflurane-fentanyl vs. propofol-remifentanil)

10% of ropivacaine group and 6% of sevoflurane

group experienced pain at 45 minutes

Rating Scale: VAS; scores unclear out of 100

Magni et al. (2009)

Italy

Prospective, double-blind RCT; N = 120

Medication: General anaesthesia

(sevoflurane vs. desflurane)

22% of sevoflurane group and 17% of desflurane

group required additional medication for pain

Rating Scale: VAS; scores unclear out of 100

Morad et al. (2009)

United States

Prospective RCT (unblinded); N = 64

Medication: as needed intravenous

fentanyl vs. PCA (fentanyl)

Patients in PCA group had significantly lower pain

scores than PRN group (2�53 vs. 3�62, respectively)

PCA group received significantly more fentanyl

Rating Scale: NRS; scores 2-4�7 out of 10

JAN: REVIEW PAPER Integrative review – postcraniotomy pain

Table 1 (Continued).

Author, year, Country Design, sample size, medication Existence of pain and pain intensity, rating scale used

Nair and Rajshekhar

(2011)

India

Prospective longitudinal study; N = 43

Medication: Oral paracetamol

5% had moderate pain in first post-op hour

Significant pain reported by 63% of patients

during first 48 hours; severe pain in 12% within

first 12 hours; incidence decreased over first

48 hours

Rating Scale: VAS; not stated out of 10

Nguyen et al. (2001)

Canada

RCT; N = 30

Medication: Scalp nerve block (ropivacaine)

70% of patients in saline group experienced

moderate pain in first 48 hours post-op

Rating Scale: VAS; scores 1�6-4�4 out of 10 Rahimi et al. (2006)

United States

Prospective, single-blinded RCT; N = 27

Medication: Oral narcotics vs. oral COX-2

inhibitors

Pain scores significantly higher in narcotics-alone

group than COX-2 group (P = 0�003) Rating Scale: VAS; scores 2-5�3 out of 10

Rahimi et al. (2010)

United States

Prospective, blinded RCT; N = 50

Medication: Oral narcotics vs. tramadol

Tramadol group had significantly lower pain scores

than narcotics-alone group (P < 0�005) Pain scores between groups significantly different

(P = 0�001435) Rating Scale: VAS; scores 1-8 (narcotics-along

group), 0-7 (tramadol group) out of 10

Saringcarinkul and

Boonsri (2008)

Thailand

Prospective, double-blind RCT; N = 50

Medication: Incisional infiltration (bupivacaine)

33% of bupivacaine group pain free at 30 minutes;

decreased to 4% at 8 hours

16% of control group pain free at 30 minutes;

decreased to 4% at 1 hour

Rating Scale: VNS; scores 2�5-3�5 out of 10 Simon et al. (2012)

Hungary

Prospective RCT; N = 90

Medication: Pre-operative oral diclofenac

Significant difference in incidence of pre-operative

headache between intervention and control

groups (P = 0�0045) 77�7% experienced pain (first post-op day); 69�4% experienced pain (fifth post-op day) Rating Scale: VAS; scores 0-9 out of 10

Sudheer et al. (2007)

Wales

Prospective RCT; N = 60

Medication: PCA (morphine vs. tramadol) vs.

intramuscular codeine

4 patients did not require additional medication in

first postoperative hour; 5 had severe pain

necessitating withdrawal from study

Less pain in morphine and codeine groups;

significant residual pain noted in tramadol group

Rating Scale: VRS; scores 0-10 out of 10

Thibault et al. (2007)

Canada

Retrospective chart review; N = 299

Medication: None tested

24% experienced mild pain, 51�5% moderate pain and 24�5% severe pain Overall prevalence of pain = 76%

Rating Scale: VRS; scores unclear out of 10

Ture et al. (2009)

Turkey

Prospective RCT; N = 80; 75 completed study

Medication: Oral gabapentin vs. oral phenytoin

Pain scores significantly higher in phenytoin group

at 15, 30 and 60 minutes (P < 0�001) Total morphine consumption significantly higher

in phenytoin group (P = 0�01) Rating Scale: VAS; scores 0-4 out of 10

Verchere et al. (2002)

France

Prospective, blind, RCT; N = 64

Medication: Paracetamol vs. paracetamol plus

tramadol vs. paracetamol plus nalbuphine

Paracetamol-only group stopped quickly due to

inadequate analgesia in 75% of patients

Rating Scale: VAS; scores 5-30 out of 100

Williams et al. (2011)

Australia

Prospective, double-blind RCT; N = 100

Medication: Intravenous parecoxib

70% of control group and 61% of parcoxib group

needed additional pain medication

Rating Scale: VAS; scores 2-5 out of 10

R.E. Guilkey et al.

Main results

As previously discussed, we used the TOUS as the guiding

framework for describing the experiences and cluster associ-

ated with postcraniotomy pain in brain tumour patients,

which resulted in five categories: (1) evidence of pain; (2)

manner of pain assessment; (3) influencing factors; (4) symp-

tom cluster and (5) patient performance (Tables 1 and 2).

Evidence of pain

Fifteen studies reported specific percentages of participants

experiencing moderate-severe pain. These percentages were

as high as 60-96% within the first 2 days after surgery,

despite the use of analgesics. Participants in eight studies

required additional pain medications and in one study,

inadequate analgesia in 75% of participants necessitated

the removal of one study arm (Verchere et al. 2002). In

this arm, six of eight patients experienced inadequate

analgesia and multiple infusions of additional pain

medication were required to reduce pain intensity scores

to below 30 (out of 100) (Verchere et al. 2002). An

additional study reported the withdrawal of five partici-

pants for severe pain in the first postoperative hour

(Sudheer et al. 2007).

Manner of pain assessment

Measures that were used to assess pain varied but most

used one-dimensional assessments of intensity including

visual analogue scales (VAS), numerical rating scales

(NRS), visual rating scales (VRS) or visual numeric

scales (VNS). Study authors did not measure other

dimensions of pain such as timing, distress, affect and

quality. Twenty-one studies (81%) identified inadequate

pain relief.

Influencing factors

Table 2 displays the evidence of postcraniotomy pain,

factors that may influence its development, an associ-

ated symptom cluster and possible impact on patient

performance. Many authors did not report all elements of

the TOUS. Eleven of the 26 studies (42%) discussed some

physiological, psychological or situational factors influenc-

ing postcraniotomy pain.

Several studies examined physiological influencing factors

such as included gender and age but findings were inconsis-

tent. One study found that women tended to experience

higher pain levels than men (Morad et al. 2009) while

another study found that men were more likely to ask for

pain medication than women (Jellish et al. 2006). The

impact of age in the development of postcraniotomy pain

also was not clear. One study found that older age was

associated with less pain (Thibault et al. 2007) while

another found increased pain levels in older patients (van

der Zwan et al. 2005).

Psychological influencing factors are the patient’s emo-

tional reactions to the disease and can include mood and

perceived level of self-sufficiency (Lenz et al. 1997, 2013).

No studies examined psychological factors that may influ-

ence the experience of postcraniotomy pain.

Situational factors are found in the social and physical

environment and can include surgical positioning, site of

surgery and use of anaesthetics. Three studies reported less

pain among patients with frontal craniotomies (Thibault

et al. 2007, Morad et al. 2009, Ducic et al. 2012) and one

study found that perioperative nerve blockade decreased the

incidence of postoperative pain (Morad et al. 2009). Gen-

eral anaesthetics used included sevoflurane and desflurane.

The use of sevoflurane resulted in less pain in one study

(Magni et al. 2005), while in another, patients receiving

sevoflurane required additional medication to control their

pain (Magni et al. 2009).

Clusters

Clusters in the TOUS are groups of co-related symptoms

that interact, affecting the patient’s symptom experience

(Lenz et al. 1997, 2013). Although the researchers did not

explicitly explore ‘symptom clusters’, 21 (81%) studies

discussed symptoms related to pain. Symptoms reported

Table 1 (Continued).

Author, year, Country Design, sample size, medication Existence of pain and pain intensity, rating scale used

van der Zwan et al. (2005)

The Netherlands

Prospective, double-blind RCT; N = 50

Medication: Remifentanil vs. fentanyl

No significant difference in pain intensity between

groups

13 of remifentanil group (45%) required

additional pain medication

Rating Scale: VAS; scores 1-4 out of 10

RCT, randomized controlled trial; 4NRS, numerical rating scale; VAS, visual analogue scale; VRS, visual rating scale; VNS, visual numeric scale.

JAN: REVIEW PAPER Integrative review – postcraniotomy pain

Table 2 Summarization of studies using theory of unpleasant symptoms concepts.

Author, Year Influencing factors Symptom cluster Patient performance

Bala et al. (2006) • Length of surgery – – Batoz et al. (2009) – • Vomiting

• Agitation • Shivering • Hypertension

–

Biswas and Bithal (2003) – • Change in diastolic blood pressure

–

Ducic et al. (2012) • Surgical site ● Altered intracranial pressure

● Altered quality of life ● Development of persistent pain

Ferber et al. (2000) – – • Change in systolic and/or diastolic blood pressure

• Changes in heart rate • Changes in partial pressure of

oxygen

• Altered intracranial pressure Girard et al. (2010) – • Nausea

• Vomiting • Change in systolic

blood pressure

–

Grossman et al. (2007) – • Nausea • Vomiting • Elevated blood

pressure

–

Irefin et al. (2003) • Gender • Surgical site

● Nausea ● Vomiting

–

Jellish et al. (2006) • Surgical approach • Gender

● Nausea ● Vomiting ● Headache

● Length of hospital stay ● Patient satisfaction ● Increased cost of medication used ● Delayed discharge from hospital

Jones et al. (2009) – • Nausea • Vomiting

● Sedation

Law-Koune et al. (2005) – • Nausea • Vomiting • Itching • Change in blood

pressure

• Bladder dysfunction

● Sedation

Magni et al. (2005) – • Nausea • Vomiting • Shivering • Change in blood

pressure

• Change in heart rate

• Change in Glasgow Coma Scale

Magni et al. (2009) – • Change in heart rate • Change in partial

pressure of oxygen

● Need for reintubation ● Changes in Glasgow Coma Scale

Morad et al. (2009) • Gender • Age • Surgical site • Surgical approach • Perioperative

neural blockade

● Nausea ● Vomiting ● Change in blood pressure ● Change in heart rate ● Change in mean arterial

pressure

● Neurological deterioration

R.E. Guilkey et al.

include headache nausea and vomiting, shivering, fatigue,

dizziness, respiratory depression, constipation, neurologic

changes, increased risk of intracranial bleeding and

agitation. The top three most common symptoms

described were nausea (15 studies; 58%), vomiting (16

studies; 62%) and changes in blood pressure including,

but not limited to, the development of hypertension (9

studies, 35%).

Table 2 (Continued).

Author, Year Influencing factors Symptom cluster Patient performance

Nair and

Rajshekhar (2011)

– • Agitation • Sympathetic Nervous

System (SNS)

stimulation

• Altered blood pressure • Brain swelling

● Development of postoperative complications

● Increased length of hospital stay ● Increased mortality rate

Nguyen et al. (2001) • Incisional site – – Rahimi et al. (2006) • Surgical site • Nausea

• Vomiting • Respiratory depression • Constipation • Neurological changes • Constipation

● Altered mental status ● Increased cost of medication used

Rahimi et al. (2010) – – • Increased cost of medication used • Increased length of hospital stay

Saringcarinkul and Boonsri (2008) – • Nausea • Vomiting

● Sedation ● Change in Glasgow Coma Scale

Simon et al. (2012) • Headache (presence prior to surgery

increased postsurgical

pain)

– • Increased length of hospital stay

Sudheer et al. (2007) • Surgical site (frontal associated with

less pain)

● Nausea ● Vomiting ● Change in partial

pressure of oxygen

–

Thibault et al. (2007) • Surgical site (frontal associated with less pain)

• Age (increased age associated with lower

pain scores)

• Muscle reflection

● Nausea ● Vomiting

–

Ture et al. (2009) – • Fatigue • Dizziness

–

Verchere et al. (2002) – • Nausea • Vomiting • Shivering • Risk of intracranial

bleeding

• Agitation • Hypertension

–

Williams et al. (2011) – • Nausea • Vomiting

● Sedation ● Change in Glasgow Coma Scale

van der Zwan et al. (2005) • Age (increasing age experienced more pain)

• Surgical site

● Nausea ● Vomiting ● Change in partial pressure

of oxygen

–

Total Studies Discussing Concept 11 21 14

NRS, numerical rating scale; VAS, visual analogue scale; VRS, visual rating scale; VNS, visual numeric scale.

JAN: REVIEW PAPER Integrative review – postcraniotomy pain

Patient performance

Patient performance is frequently assessed in terms of

tangible functional outcomes, such as length of stay, readi-

ness to be discharged and perceived quality of life.

Although performance related to postcraniotomy pain was

not explicitly examined, almost half of the studies described

potential results of postcraniotomy pain (Table 2). How-

ever, it was unclear if the impact on patient performance

was a direct result of pain, the use of pain medication, or

other factors. Other functional performance outcomes

reported included increased cost of medication and

increased hospital length-of-stay. In two different studies,

poorly managed postcraniotomy pain resulted in delayed

discharge and altered quality of life (Jellish et al. 2006,

Ducic et al. 2012). Four studies described changes in cogni-

tive performance using the proxy measure of level of con-

scious assessed by the Glasgow Coma Scale (GCS) (Magni

et al. 2005, Saringcarinkul & Boonsri 2008, Magni et al.

2009, Williams et al. 2011). Two studies found changes in

level of consciousness due to type and amount of analgesic

used (Saringcarinkul & Boonsri 2008, Williams et al. 2011)

and one identified these changes as being the result of

uncontrolled pain (Magni et al. 2005).

Discussion

To our knowledge, this is the first integrative review of

data-based studies examining: (1) evidence for postcran-

iotomy, postbrain tumour pain; and (2) the evidence for a

postcraniotomy pain symptom cluster in brain tumour

patients. Brain tumours affect many worldwide and pain

has been identified as a public health priority. Accordingly,

most research on postcraniotomy pain has been conducted

in other countries. Research to date has focused solely on

pharmacological intervention and fails to explore the multi-

dimensional nature of pain through comprehensive assess-

ment (Leslie & Troedel 2002, Nemergut et al. 2007,

Hansen et al. 2011, Guilfoyle et al. 2013). Although phar-

macological interventions exist, no one therapeutic medica-

tion has been identified as most efficacious (National

Pharmaceutical Council 2003, Paolino et al. 2006, Institute

of Medicine Committee on Advancing Pain Research, C.

and Education 2011, Saha et al. 2013). Our review found

that despite the use of 18 different analgesics, moderate to

severe pain still occurred among postcraniotomy brain

tumour patients and that many patients expressed inade-

quate pain management resulting in the need for more anal-

gesics. This review provides strong evidence for the

existence of postcraniotomy pain and the need for more

research to develop evidence-based practice guidelines in

this population.

While researchers have begun to study patients’ subjective

experiences after craniotomy, such as their fears, expecta-

tions and satisfaction (Khu et al. 2010, Milian et al. 2014),

these investigations have not yet addressed pain. Patients’

experiences of pain will necessarily be affected by amount

of pain control and healthcare provider interaction, but the

extent to which these influence postcraniotomy, postbrain

tumour patient experience has not yet been made clear.

Due to the complicated nature of postcraniotomy pain, fur-

ther research is warranted to provide evidence-based care.

A full understanding of the postcraniotomy pain experi-

ence from the patients’ perspectives would improve assess-

ment of pain, planning of interventions and evaluation of

care (Melzack 1999, Andrasik et al. 2011, Watt-Watson &

McGillion 2011). This review serves as a call to action to

describe the context and unfolding of postcraniotomy brain

tumour pain from the patient’s perspective and provides

evidence to challenge the commonly held belief that

postcraniotomy pain is not an important problem (Has-

souneh et al. 2010, American Brain Tumor Association

2012).

The intensity of postcraniotomy, postbrain tumour pain

is well-documented. Measures such as VASs are capable of

reflecting this intensity and change in pain over time (Jensen

& Karoly 2011). However, pain intensity is not necessarily

correlated with level of patient distress and resulting patient

performance (Melzack 1999, Jensen & Karoly 2011, Turk

& Melzack 2011, Turk & Robinson 2011, Watt-Watson &

McGillion 2011). Consequences such as the development of

dysfunction and disability reflect broader dimensions of

pain that cannot be assessed by mere measures of intensity

and distress (Turk & Melzack 2011, Watt-Watson &

McGillion 2011). Current research fails to explore the pain

experience beyond intensity and does not address the clus-

ter of associated symptoms that may magnify pain and/or

moderate treatment effects.

The limited and conflicting nature of the evidence con-

cerning physiological factors that influence the development

of postcraniotomy pain in the brain tumour patient suggests

that additional, more comprehensive description is needed.

Increased awareness of the experiences of postcraniotomy

pain across age groups is needed (Andrasik et al. 2011).

Investigations of the experience of postcraniotomy, post-

brain tumour pain by gender could lead to the development

of targeted approaches for men and women. Similarly,

while incidence of brain tumour is higher in Caucasians

than in those of other racial backgrounds (National Cancer

Institute 2014), few authors report racial characteristics of

R.E. Guilkey et al.

the study sample, preventing clear understanding of the

manner in which postcraniotomy pain unfolds among

different groups.

Psychological factors influencing the development of

postcraniotomy, postbrain tumour pain are also thought to

be important (McCaffery & Pasero 1999, Melzack 1999

Andrasik et al. 2011, Turk & Robinson 2011, Lenz et al.

2013). None of the studies in the review, however,

addressed these factors and thus it is not yet clear what role

emotions, mood and perceived level of self-sufficiency play

in the unfolding and experience of postcraniotomy pain.

Situational factors that affect the unfolding and experi-

ence of postcraniotomy pain also need further clarification.

Longer surgical time influences length of intensive care unit

stays in cardiac patients (Chu et al. 2008) and length of

surgery influences the severity of postoperative pain in

ambulatory care surgical patients (Chung et al. 1997). In

postcraniotomy patients, longer surgeries may increase post-

surgical pain due to greater time spent in surgical positions,

increased duration of muscle retraction, larger incisions and

the potential for more involved surgical procedures (Casler

et al. 2005, Ducic et al. 2012). Researchers should there-

fore investigate the impact of length of surgery on the

development of postcraniotomy pain.

More detailed comparisons could also be made if surgical

diagnoses were consistently reported. For example, it is

known that postoperative headache in occipital surgeries

stems from resulting occipital neuralgia (Ducic et al. 2012).

Examining the effect of surgical location on development of

postcraniotomy headache could lead to better targeted

interventions.

The existence of a symptom cluster would call for com-

prehensive postcraniotomy pain assessment (Melzack 1999

Andrasik et al. 2011, Saha et al. 2013). Little is known,

however, about the cluster associated with postcraniotomy,

postbrain tumour pain. In the current science, effects of

pharmaceutical interventions, postcraniotomy pain, other

symptoms such as pain and anxiety and patient perfor-

mance are often confounded. Research that explicates the

nature of symptom clusters in this population is needed.

Literature shows that postoperative pain may affect

performance by increasing length of stay, cost of hospital-

ization and delaying discharge (Watt-Watson & McGillion

2011, Saha et al. 2013). Some research links postcran-

iotomy pain to increased length of stay and delayed readi-

ness to be discharged in the traumatic head injury

population (Honeybul 2010, Honeybul & Ho 2010).

However, only a few studies have examined the impact of

postcraniotomy pain on brain tumour patients’ functional

and cognitive performance.

In the broader pain literature, untreated acute pain has

been correlated with the development of long-term pain

due to nervous system plasticity (Melzack 1999, Turk &

Robinson 2011, Watt-Watson & McGillion 2011, Ducic

et al. 2012). In addition, researchers of general postsurgical

pain have shown that inadequate postoperative analgesia

has led to the development of persistent pain (Horn &

Munafo 1997, McCaffery & Pasero 1999, Watt-Watson &

McGillion 2011). Batoz et al. (2009) have shown that

improved pain management in postcraniotomy patients

during the acute postoperative period decreases the devel-

opment of persistent pain at 2 months, but the relationship

between postoperative pain management and persistent

pain has not been well-studied in postcraniotomy brain

tumour patients. Therefore, describing the connection

between postcraniotomy pain and patient performance

could lead to the development of interventions to prevent

or minimize both postcraniotomy pain and its resulting

effects.

Over 40 years of research have repeatedly illustrated that

pain is under-assessed, under-recognized and undertreated.

The treatment of postcraniotomy pain is further compli-

cated by a lack of understanding of the manner in which it

unfolds over the course of the postoperative period and a

reluctance to treat it aggressively for fear of masking neuro-

logical changes. The result is an unclear risk-benefit ratio

associated with the treatment of postcraniotomy pain in

brain tumour patients. Additional research would illuminate

the relationship between postcraniotomy pain, influencing

factors, associated clusters and patient performance, leading

to the development of timely interventions to control pain

without increasing risk to patients.

Limitations

This review was limited to examining studies that discussed

particular influencing factors, associated clusters and the

effect of postcraniotomy, postbrain tumour pain on patient

performance. It is possible that studies looking at postcran-

iotomy pain in a different context were missed. In addition,

this review does not represent ongoing or unpublished

studies, nor does it include published work that has not

undergone the peer review process.

Conclusion

Evidence suggests that postcraniotomy, postbrain tumour

patients experience significant postsurgical pain but no

guidelines have been established to treat this pain. Postcran-

iotomy pain may influence length of hospital stay, cost of

JAN: REVIEW PAPER Integrative review – postcraniotomy pain

medications, quality of life and development of persistent

pain. However, little research has been conducted on the

complex nature and experience of postcraniotomy, post-

brain tumour pain. Mitigating or preventing postcran-

iotomy pain in the brain tumour population will likely

result in improved patient outcomes. Patient-centred out-

comes research should focus on attempting to understand

postcraniotomy pain, which will pave the way for the

development of timely interventions and standardization of

treatment for postcraniotomy pain to improve functional

outcomes and quality of life.

Acknowledgement

The authors thank and acknowledge the T32 programme

leadership of Dr. Susan Rawl.

Funding

The work reported in this publication was supported by the

National Institute of Nursing Research of the National

Institutes of Health under Award Number T32NR007066.

The content is solely the responsibility of the authors and

does not necessarily represent the official views of the

National Institutes of Health. This work was also sup-

ported by a Jonas Leadership Scholarship from the Jonas

Center for Nursing Excellence, and the Irene and Nathaniel

Aycock Scholarship and the Cheryl A. Bean Scholarship

from the Indiana University School of Nursing.

Conflict of interest

The authors had no conflicts of interest.

Author contributions

All authors have agreed on the final version and meet at

least one of the following criteria [recommended by the

ICMJE (http://www.icmje.org/recommendations/)]:

� substantial contributions to conception and design, acquisition of data or analysis and interpretation of

data;

� drafting the article or revising it critically for impor- tant intellectual content.

Supporting Information

Additional Supporting Information may be found in the

online version of this article at the publisher’s web-site.

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